Efficacy and Safety of Dapagliflozin in Children With Proteinuric Chronic Kidney Disease
Study Details
Study Description
Brief Summary
We aim to investigate the antiproteinuric effect of adding Dapagliflozin to the standard of care in children with proteinuria.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Blockers of renin angiotensin aldosterone system (RAAS) such as angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) are considered the standard of care in treatment of Proteinuric Chronic Kidney Disease. However, these agents lead to incomplete renal protection. The purpose of the study is to investigate the antiproteinuric effect of adding Dapagliflozin to the standard of care in children with proteinuria. In this study, participants were randomly assigned (1:1) to receive ACEI+Dapagliflozin (5mg or 10mg, based on body weight) or ACEI only once daily for 24 weeks. Prespecified outcomes includes changes in 24-hr proteinuria, albumin, eGFR (estimated glomerular filtration rate), blood pressure, body weight and so on.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: ACEI treatment Drug: ACEI will be given once daily |
Drug: ACEI treatment
ACEI, will be given once daily based on body weight (0.2mg/kg/d-0.6mg/kg/d，max 20mg/d), for 24 weeks
Other Names:
|
| Experimental: Dapagliflozin+ACEI treatment Drug: ACEI, will be given once daily Drug: Dapagliflozin, will be given once daily |
Drug: Dapagliflozin+ACEI treatment
Dapagliflozin will be given 10 mg/day (weight>30kg) or 5mg/day (weight≤30kg), for 24 weeks ACEI, will be given based on body weight (max 20mg/d), for 24 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The change in 24 hour proteinuria [From baseline to week 12]
Urine will be collected for 24 hours and total urinary albumin excretion will be measured
Secondary Outcome Measures
- The change in 24 hour proteinuria [From baseline to week 24]
Urine will be collected for 24 hours and total urinary albumin excretion will be measured
- The change in albumin from baseline to week 24 [Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24]
Serum albumin levels are repeated measurement data
- The change in eGFR (estimated glomerular filtration rate) from baseline to week 24 [Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24]
eGFR will be evaluated using Schwartz formula (eGFR=k*height(cm)/serum creatinine(umol/L)), k=36.5), and eGFR are repeated measurement data
- The change blood pressure from baseline to week 24 [Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24]
Blood pressure including systolic blood pressure (SBP) and diastolic blood pressure (DBP) are repeated measurement data
- The change in body weight from baseline to week 24 [Measured at baseline, weeks 4, weeks 8, weeks 12, weeks 24]
Body weight are repeated measurement data and will be measured in the morning
- The number of hypoglycemia episodes during the treatment [From baseline to week 24]
Patients will be asked to measure fasting blood glucose every morning and record the data by their parents during the treatment period. Hypoglycemia is defined as glucose level less than 3.9mmol/L.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age 6 years to 18 years；
-
Urinary protein excretion > 200 mg in a 24-hr urine collection；
-
Without any immunosuppressant medications such as corticosteroids, CNIs and so on；
-
Estimated GFR ≥ 60 ml/min/1.73m2（estimated with Schwartz formula）；
-
No history of diabetes；
-
On stable doses of ACE inhibitors or angiotensin receptor blockers (ARBs) for > 1 month；
-
Willing to sign informed consent.
Exclusion Criteria:
-
Autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis;
-
Blood pressure less than 5th percentile of the same gender, age, and height;
-
Uncontrolled urinary tract infection at screening;
-
At risk for dehydration or volume depletion;
-
Evidence of hepatic disease: an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) two times the upper limit of normal
-
History of organ transplantation, cancer, liver disease;
-
Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:
-
History of active inflammatory bowel disease within the last six months;
-
Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
-
Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
-
Pancreatic injury or pancreatitis within the last six months;
-
Participation in another therapeutic trial with an investigational drug within 30 days prior to informed consent;
-
History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Fudan University | Shanghai | Shanghai | China | 201102 |
Sponsors and Collaborators
- Children's Hospital of Fudan University
Investigators
- Study Director: Qian Shen, Profressor, Children's Hospital of Fudan University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EASOD.01